Aldolase Antibodies of Remarkable Scope

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• 作者：Torsten Hoffmann ; Guofu Zhong ; Benjamin List ; Doron Shabat ; James Anderson ; Svetlana Gramatikova ; Richard A. Lerner ; and Carlos F. Barbas ; III
• 刊名：Journal of the American Chemical Society
• 出版年：1998
• 出版时间：April 1, 1998
• 年：1998
• 卷：120
• 期：12
• 页码：2768 - 2779
• 全文大小：271K
• 年卷期：v.120,no.12(April 1, 1998)
• ISSN：1520-5126

文摘

This paper describes the substrate specificity, synthetic scope,and efficiency of aldolase catalyticantibodies 38C2 and 33F12. These antibodies use the enaminemechanism common to the natural Class Ialdolase enzymes. Substrates for these catalysts, 23 donors and 16acceptors, have been identified. The aldolacceptor specificity is expected to be much broader than that definedhere since all aldehydes tested, with theexception polyhydroxylated aldehydes, were substrates for theantibodies. 38C2 and 33F12 have been shownto catalyze intermolecular ketone-ketone, ketone-aldehyde,aldehyde-ketone, and aldehyde-aldehyde aldoladdition reactions and in some cases to catalyze their subsequentdehydration to yield aldol condensationproducts. Substrates for intramolecular aldol reactions have alsobeen defined. With acetone as the aldoldonor substrate a new stereogenic center is formed by attack on thesi-face of the aldehyde with ee's in mostcases exceeding 95%. With hydroxyacetone as the donor substrate,attack occurs on the re-face, generatingan mages/gifchars/alpha.gif" BORDER=0>,mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-dihydroxy ketone with two stereogenic centers of the mages/gifchars/alpha.gif" BORDER=0>-synconfiguration in 70 to >98% ee. Withfluoroacetone donor reactions, the major product is a synmages/gifchars/alpha.gif" BORDER=0>-fluoro-mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-hydroxy ketone with 95% ee. Studiesofretroaldol reactions demonstrate that the antibodies provide up to10⁸-fold enhanced efficiency relative tosimple amine-catalyzed reactions.